The impact of disease modifying therapies on cognitive functions typically impaired in multiple sclerosis patients: a clinician's review.

Objective: Over the last few decades clinicians have become aware that cognitive impairment might be a major cause of disability, loss of employment and poor quality of life in patients suffering from multiple sclerosis [MS].The impact of disease modifying therapies [DMTs] on cognition is still a matter of debate. Theoretically, DMTs could exert a substantial beneficial effect by means of reducing neuroinflammation and brain atrophy, which are established correlates of cognitive dysfunction. The aim of the study was to review the evidence concerning the effect of DMTs on cognitive functions. Methods: PubMed, Scopus, and the European Committee for Treatment and Research in Multiple Sclerosis [ECTRIMS] Library were searched for articles concerning the pediatric and adult populations of patients with multiple sclerosis, including clinical trials and RWD, where psychometric results were analyzed as secondary or exploratory endpoints. Results: We reviewed a total of 44 studies that were found by our search strategy, analyzed the psychological tests that were applied, the length of the follow-up, and possible limitations. We pointed out the difficulties associated with assessing of DMTs' effects on cognitive functions, and pitfalls in cognitive tools used for evaluating of MS patients. Conclusion: There is a need to highlight this aspect of MS therapies, and to collect adequate data to make informed therapeutic decisions, to improve our understanding of MS-related cognitive dysfunction and provide new therapeutic targets.

Prevalence and prognostic value of prodromal symptoms in relapsing-remitting multiple sclerosis.

INTRODUCTION: Several studies have suggested the possibility that disease prodromes might occur months or even years before a multiple sclerosis diagnosis. OBJECTIVES: To describe the profile of prodromal symptoms and the possible relationship between the occurrence of individual symptoms and clinical course characteristics in patients with relapsing-remitting multiple sclerosis (RRMS), and to assess their role as predictors of further disease course. MATERIAL AND METHODS: The cohort included 564 patients with RRMS. Patients were stratified based on their current EDSS score, and the annual EDSS growth rate was calculated. Logistic Regression Analysis was used to study the relationship between prodromal symptoms and disease progression. RESULTS: The most commonly reported prodromal symptom was fatigue (42%). The following symptoms were significantly more common in women than in men: headache (39.7% vs. 26.5%, p < 0.05), excessive sleepiness (19.1% vs. 11.1%, p < 0.05) and constipation (18.0% vs. 11.1%, p < 0.05). Prodromal urinary and cognitive disturbances, fatigue and pain complaints were significantly more common in patients with the highest annual EDSS increase (p < 0.05). Multivariate analysis revealed some potential predictors of long-term disability progression: hesitancy in starting urination predicted EDSS increase by 0.6 point (p < 0.05), while deterioration in everyday functioning because of cognitive disturbances, and pain complaints, were associated with an EDSS increase of 0.5 (p < 0.05), and 0.4 (p < 0.05), respectively. CONCLUSIONS: Prodromal pain, urinary and cognitive complaints (especially when these lead to deterioration of everyday functioning) were associated with a higher EDSS increase rate, and may thus be regarded as possible predictors of worse clinical outcomes in RRMS patients.

Case Report: Baló's Concentric Sclerosis-Like Lesion in a Patient With Relapsing-Remitting Multiple Sclerosis Treated With Dimethyl Fumarate.

Baló's concentric sclerosis (BCS) is a rare demyelinating disorder characterized by acute or subacute neurological symptoms associated with characteristic lesions of concentric onion skin appearance on MRI images and in pathology. The connection between BCS and classic MS is still a subject of debates. Our report presents a case of a patient who developed a symptomatic Baló-like lesion following several years of classical relapsing-remitting multiple sclerosis treated with dimethyl fumarate.

Acute disseminated encephalomyelitis in a patient vaccinated against SARS-CoV-2.

Acute disseminated encephalomyelitis (ADEM) is a demyelinating disease, and there are some data that link this event with various vaccinations. We report a young female admitted to the hospital with headache, fever, back pain, nausea, vomiting, and urinary retention. Two weeks prior, she received the first dose of SARS-CoV-2 mRNA vaccine. Brain and spinal cord magnetic resonance imaging (MRI) showed distinctive for ADEM widespread demyelinating lesions. The patient was successfully treated with methylprednisolone.

Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease: Current Insights into the Disease Pathophysiology, Diagnosis and Management.

Myelin oligodendrocyte glycoprotein (MOG)-associated disease (MOGAD) is a rare, antibody-mediated inflammatory demyelinating disorder of the central nervous system (CNS) with various phenotypes starting from optic neuritis, via transverse myelitis to acute demyelinating encephalomyelitis (ADEM) and cortical encephalitis. Even though sometimes the clinical picture of this condition is similar to the presentation of neuromyelitis optica spectrum disorder (NMOSD), most experts consider MOGAD as a distinct entity with different immune system pathology. MOG is a molecule detected on the outer membrane of myelin sheaths and expressed primarily within the brain, spinal cord and also the optic nerves. Its function is not fully understood but this glycoprotein may act as a cell surface receptor or cell adhesion molecule. The specific outmost location of myelin makes it a potential target for autoimmune antibodies and cell-mediated responses in demyelinating processes. Optic neuritis seems to be the most frequent presenting phenotype in adults and ADEM in children. In adults, the disease course is multiphasic and subsequent relapses increase disability. In children ADEM usually presents as a one-time incident. Luckily, acute immunotherapy is very effective and severe disability (ambulatory and visual) is less frequent than in NMOSD. A critical element of reliable diagnosis is detection of pathogenic serum antibodies MOG with accurate, specific and sensitive methods, preferably with optimized cell-based assay (CBA). MRI imaging can also help in differentiating MOGAD from other neuro-inflammatory disorders. Reports on randomised control trials are limited, but observational open-label experience suggests a role for high-dose steroids and plasma exchange in the treatment of acute attacks, and for immunosuppressive therapies, such as steroids, oral immunosuppressants and rituximab as maintenance treatment. In this review, we present up-to-date clinical, immunological, radiographic, histopathological data concerning MOGAD and summarize the practical aspects of diagnosing and managing patients with this disease.

Association of platelet-derived microvesicles and their phenotypes with carotid atherosclerosis and recurrent vascular events in patients after ischemic stroke.

INTRODUCTION: Platelet-derived microvesicles (pMVs) exhibit procoagulant and proinflammatory properties and play a role in the development and progression of atherosclerosis. The study examined the association between the total number of pMVs and their phenotypes with carotid atherosclerosis and recurrent vascular events (VEs) in patients in the convalescent phase of ischemic stroke (IS). MATERIALS AND METHODS: The study group consisted of 72 patients with IS secondary to large artery atherosclerosis (LAA) (n = 40) and small arteries occlusion (SAO) (n = 32) and 69 matched cardiovascular disease risk-factor (RF) controls. Total pMV number, defined as CD61+ microvesicles (MVs), and their phenotypes, defined as the surface expression of proinflammatory (CD40L, CD62P, CD31) and procoagulant (PS, PAC-1) markers, were characterized and quantified using flow cytometry. The mean common carotid intima-media thickness (CCA mean IMT), maximal common carotid IMT (CCA max IMT) and maximal bifurcation IMT (BIF max IMT) were measured bilaterally using B-mode, color Doppler ultrasonography. All study subjects were observed for one-year to establish the occurrence of VEs. RESULTS: No differences in pMV parameters between LAA and SAO stroke subjects and between stroke subgroups and controls were found. Stroke patients with carotid atherosclerosis exhibited higher concentration of CD62P+/CD61+ and PAC-1+/CD61+ MVs compared to patients without the atherosclerosis. Positive associations between total number of pMVs, AnV+ MVs and AnV+/CD61+ MVs and atherosclerotic thickening of carotid intima-media in stroke patients were found. Elevated concentration of AnV+/CD61+, PAC-1+/CD61+, CD61P+/CD61+ and CD31+/CD61+ MVs, were revealed in stroke patients who suffered from recurrent VE in one-year follow-up period. Negative correlation of pMVs and CD62P+/CD61+ MVs concentration as well as percentage of total CD61+ in AnV+ population of MVs and time elapsed from IS in convalescent stroke subjects was revealed. CONCLUSION: Our results confirm positive correlations between total pMV number, the number of PAC-1+/CD61+ and CD62+/CD61+ MVs and carotid atherosclerosis in stroke subjects. Some pMV parameters may exhibit a predictive value for the next VE in groups with a history of stroke. pMVs and some of their phenotypes decline over time elapsed from stroke in convalescent stroke subjects.

With a subarachnoid haemorrhage, the outcome is never enough.

INTRODUCTION: In the current edition, Nastasovic et al. present the results of a prospective study on patients with aneurysm subarachnoid haemorrhage (SAH) regarding the association of selected variables and outcomes three months after the incident. CLINICAL REFLECTIONS: The independent predicting factors of an unfavourable aneurysm SAH outcome are aneurysm re-rupture, high systolic blood pressure (SBP), and increased heart rate. CLINICAL IMPLICATIONS: The article findings confirm easily monitored parameters that could be potentially useful in clinical approaches to this critical illness.

Free thyroxine and TSH interact with secreted protein acidic and rich in cysteine-like 1 in ischemic stroke.

The role of the thyroid gland in ischemic stroke pathology is not well understood. As thyroid hormones modulate the extracellular matrix, we explored the possible link between them and secreted protein acidic and rich in cysteine like 1 (SC1) - one of the extracellular matrix molecules. In the 81 patients with acute ischemic stroke, serum SC1 levels were much higher compared with 30 control subjects: 4.47 vs 2.43ng/mL (p<0.001). Serum levels of free thyroxine (fT4) were higher in stroke subjects compared to those of controls (p=0.03). In stroke patients, TSH concentration was lower than in the control group (p=0.03). SC1 levels positively correlated with fT4 levels (p=0.02) and negatively with TSH (p=0.03) in stroke patients. Our results confirmed the association between thyroid hormones and SC1 - extracellular matrix protein.

The Association between Serum Matricellular Protein: Secreted Protein Acidic and Rich in Cysteine-Like 1 Levels and Ischemic Stroke Severity.

BACKGROUND: The role of matricellular proteins like secreted protein acidic and rich in cysteine-like 1 (SC1) has been shown in important functions in the central nervous system, including the regulation of synaptic stability with upregulation throughout axonal regeneration. The aim of this study was to determine whether SC1 is related to ischemic stroke severity. METHODS: A total of 132 consecutively recruited patients admitted for acute ischemic stroke were included in this observational prospective study. Stroke severity was evaluated in the National Institutes of Health (NIHSS) scale on hospital admission. RESULTS: There was a positive correlation between SC1 levels and NIHSS score (r = .22, P = .009). Compared with patients with NIHSS scores lower than 5 at admission, patients with moderate and severe stroke (NIHSS ≥ 6) had significantly higher SC1 levels: 4.84 (2.53-11.58) ng/mL versus 3.31 (1.67-8.95) ng/mL (P = .01). SC1 was an independent predictor of stroke severity at admission (adjusted odds ratio =1.25; 95% confidence interval, 1.03-1.97; P = .04). CONCLUSION: SC1 levels were independently associated with ischemic stroke severity evaluated by the NIHSS.

Mitochondrial Respiration in Intact Peripheral Blood Mononuclear Cells and Sirtuin 3 Activity in Patients with Movement Disorders.

OBJECTIVE: Mitochondrial dysfunction is considered a unifying pathophysiological explanation for movement disorders. Sirtuin 3 (SIRT3) exhibits deacetylase activity and antioxidant properties. The aim of the study was to analyze the mitochondrial respiration in peripheral blood mononuclear cells (PBMCs) and the SIRT3 activity in patients with movement disorders. METHODS: Mitochondrial respiration was analyzed in intact PBMCs using the ROUTINE, LEAK, electron transfer system (ETS), and residual oxygen consumption (ROX) protocol by means of high-resolution respirometry. The SIRT3 expression and PBMC activity were measured using fluorometry. Ultrasound measurements of the echogenicity of the substantia nigra and the diameter of the 3rd ventricle were also performed. RESULTS: Patients with movement disorders exhibited a lower ROUTINE respiration than controls (P = 0.0237). Reduced oxygen fluxes in the LEAK (P = 0.033) and ROX (P = 0.0486) states were observed in patients with movement disorders compared with controls. Decreased ROUTINE respiration (P = 0.007) and oxygen flux in the LEAK state (P = 0.0203) were observed in patients with PD with substantia nigra hyperechogenicity compared with controls. Decreased SIRT 3 deacetylase activity was found in patients with movement disorders. CONCLUSION: Impaired mitochondrial respiration in intact PBMCs was associated with inhibited SIRT3 activity and neurodegeneration measures evaluated using ultrasound in patients with PD.

Predictive value of serum transthyretin for outcome in acute ischemic stroke.

INTRODUCTION: The impact of choroid plexus with its blood-cerebrospinal fluid barrier in the ischemic stroke pathology is poorly explored. Transthyretin (TTR) is a protein synthesized in liver and just in choroid plexus. OBJECTIVES: The current study was designed to assess the prognostic value of serum TTR for functional outcome (at the time of hospital discharge) and long-term (one-year) overall mortality in ischemic stroke patients. PATIENTS AND METHODS: We conducted a prospective observational study. Patients (n = 81) with acute (< 24 hours of symptoms onset) ischemic stroke consecutively admitted to Stroke Unit were included. An unfavorable outcome was defined as a modified Rankin Scale (mRS) score ≥ 3. The relationships between serum TTR levels and clinical outcome were analyzed using multivariate analysis. One-year mortality was analyzed by Kaplan-Meier survival curves stratified by mean value of TTR. RESULTS: Compared with patients with mRS <3, patients with an unfavorable outcome at hospital discharge had significantly lower TTR levels on admission (P < 0.0001). In non-survivals serum TTR levels were significantly lower compared with patients who survive one year of observation (P = 0.009). Using multivariate analysis, transthyretin emerged as an independent predictor for unfavorable outcome at the day of hospital discharge (adjusted odds ratio = 0.96; 95% CI: 0.9-0.99, P <0.05). A one-year mortality of patients with the lower TTR levels was significantly higher than in patients with TTR levels above mean value (P = 0.02). CONCLUSIONS: Serum level of TTR at admission was a predictor of functional outcome after ischemic stroke and was also associated with one-year mortality in stroke survivals.

The Markers of Glutamate Metabolism in Peripheral Blood Mononuclear Cells and Neurological Complications in Lung Cancer Patients.

Objective. To evaluate the involvement of glutamate metabolism in peripheral blood mononuclear cells (PBMC) in the development of neurological complications in lung cancer and during chemotherapy. Methods. The prospective study included 221 lung cancer patients treated with chemotherapeutics. Neurological status and cognitive functions were evaluated at baseline and after 6-month follow-up. Glutamate level, the activities of glutaminase- (GLS-) glutamate synthetizing enzyme, glutamate dehydrogenase (GDH), and glutamate decarboxylase catalyzing glutamate degradation were analyzed in PBMC and in sera of lung cancer patients by means of spectrophotometric and colorimetric methods. Results. Chemotherapy of lung neoplasms induced increase of glutamate content in PBMC and its concentration in serum increased the activity of GDH in PBMC and decreased activity of glutaminase in PBMC. The changes in glutamate metabolism markers were associated with initial manifestation of neurological deficit in lung cancer patients and with new symptoms, which appear as a complication of chemotherapy. Moreover, the analyzed parameters of glutamate control correlated with a spectrum of cognitive functions measures in lung cancer patients. Conclusion. We have demonstrated dysregulation in glutamate and glutamate metabolism controlling enzymes as promising indicators of risk for chemotherapy-induced neurological complications in lung cancer patients with particular emphasis on cognitive impairment.

The Early Effect of Carotid Artery Stenting on Antioxidant Capacity and Oxidative Stress in Patients with Carotid Artery Stenosis.

The treatment of carotid artery stenosis is associated with the risk of complications, which may include stroke after carotid artery stenting (CAS) and myocardial infarction after carotid endarterectomy (CEA). The imbalance between prooxidative mechanisms and antioxidant capacity creates a milieu of factors, which may increase the risk of complications after endovascular procedures. We have examined 43 consecutive patients with carotid artery stenosis. Sera were analyzed for the activity of paraoxonase (PON) and arylesterase (ARE), sulfhydryl groups (SG), malondialdehyde (MDA), and conjugated dienes (CD) concentrations by means of spectrophotometric methods before and next day after CAS. We have found lowered PON (P = 0.0032), increase in ARE activity (P = 0.0058), and decrease in sulfhydryl groups concentration (P = 0.0267). No effect on absolute MDA and CD concentrations was observed. The degree of carotid artery stenosis correlated negatively with PON/ARE ratio after CAS (rS = -0.507, P = 0.0268). To conclude, CAS influences both enzymatic (differently, PON and ARE activity) and nonenzymatic antioxidant defense. Females are more susceptible to lipid peroxidation after CAS. PON/ARE ratio after CAS correlated with the degree of carotid artery stenosis. The changes (deltas) in ARE activity, SG, and MDA concentrations correlated with the severity of neurological deficit and disability.

Population-based Stroke Atlas for outcome prediction: method and preliminary results for ischemic stroke from CT.

BACKGROUND AND PURPOSE: Knowledge of outcome prediction is important in stroke management. We propose a lesion size and location-driven method for stroke outcome prediction using a Population-based Stroke Atlas (PSA) linking neurological parameters with neuroimaging in population. The PSA aggregates data from previously treated patients and applies them to currently treated patients. The PSA parameter distribution in the infarct region of a treated patient enables prediction. We introduce a method for PSA calculation, quantify its performance, and use it to illustrate ischemic stroke outcome prediction of modified Rankin Scale (mRS) and Barthel Index (BI). METHODS: The preliminary PSA was constructed from 128 ischemic stroke cases calculated for 8 variants (various data aggregation schemes) and 3 case selection variables (infarct volume, NIHSS at admission, and NIHSS at day 7), each in 4 ranges. Outcome prediction for 9 parameters (mRS at 7th, and mRS and BI at 30th, 90th, 180th, 360th day) was studied using a leave-one-out approach, requiring 589,824 PSA maps to be analyzed. RESULTS: Outcomes predicted for different PSA variants are statistically equivalent, so the simplest and most efficient variant aiming at parameter averaging is employed. This variant allows the PSA to be pre-calculated before prediction. The PSA constrained by infarct volume and NIHSS reduces the average prediction error (absolute difference between the predicted and actual values) by a fraction of 0.796; the use of 3 patient-specific variables further lowers it by 0.538. The PSA-based prediction error for mild and severe outcomes (mRS  =  [2]-[5]) is (0.5-0.7). Prediction takes about 8 seconds. CONCLUSIONS: PSA-based prediction of individual and group mRS and BI scores over time is feasible, fast and simple, but its clinical usefulness requires further studies. The case selection operation improves PSA predictability. A multiplicity of PSAs can be computed independently for different datasets at various centers and easily merged, which enables building powerful PSAs over the community.

Automatic detection, localization, and volume estimation of ischemic infarcts in noncontrast computed tomographic scans: method and preliminary results.

OBJECTIVES: Sensitivity of noncontrast computed tomography (NCCT) in detecting hyperacute (< 8 hours) and acute (< 24 hours) cerebral infarction is low. We propose an automatic method to detect and localize ischemic infarct and to assess its volume from a single NCCT scan. MATERIALS AND METHODS: The method automatically determines attenuation value ranges of cerebrospinal fluid and white and gray matter, separates the brain scan into the left and right hemispheres, and by analyzing hemisphere attenuation value distributions using percentile difference ratios, it detects, localizes, and quantifies the infarct without its segmentation. The method performance was evaluated on 576 patients with clinically confirmed stroke through NCCT scans acquired at 4 centers to measure how it matched with that of experts in detection, localization, and assessment of infarct volume. The time from the onset of symptoms ranged from 1.5 to 72 hours for 450 scans and more than 72 hours for 82 scans, most with pathologic findings in addition to cerebral infarction; the time was unavailable for 44 scans. In addition, the method was compared with the novice's (with 52 scans) and experienced readers' infarct detection (with 21 × 2 scans) in early ischemia detection (with the time from the onset of symptoms ranging from 1.5 to 7 hours). RESULTS: The method matches 100% the expert's infarct detection when chronic infarcts, leukoaraiosis cases, and infarct volumes less than 2 cm (determined by detection accuracy simulation) are excluded from the analysis. For all cases excluding infarct volumes less than 2 cm, the method detection accuracy is 95.7%. Overall, the method detection accuracy is 83.2%. The early method detection accuracy (≤ 3 hours) is 78.4%. The novice detection accuracy is 27.8% (≤ 3 hours), 37.5% (3 < to ≤ 8 hours), and 77.8% (> 8 hours), whereas the expert detection accuracy for these cases is 100%. Moreover, the method detected all 21 early infarcts, of which 15 were missed by the stroke experts and 14 of 15 were missed by a general radiologist. The method performs automatic analysis in approximately 7 seconds. CONCLUSIONS: The results demonstrate potential benefits of our method for enhancing expert's performance because it quickly localizes the infarct and detects cases missed by experts, and it is to be considered as an aid in the emergency department because it substantially outperforms novice readers (100% vs 27%) in infarct detection on NCCT.

Enhanced platelet-derived microparticle formation is associated with carotid atherosclerosis in convalescent stroke patients.

Platelets participate in the development and progression of atherosclerosis. During this process they interact with endothelial cells and leukocytes. Therefore, we investigated the associations between carotid atherosclerosis and platelet reactivity markers. The platelet surface expression of P-selectin (CD62P) and the activated GPIIb/IIIa receptor (corresponding to increased binding of PAC-1), as well as the fraction of platelet-derived microparticles (PMPs) prior to and after platelet stimulation with TRAP or ADP, were determined using flow cytometry in 94 subjects in the convalescent phase of ischaemic stroke and in 76 disease controls. The mean common carotid intima-media thickness (CCA(mean) IMT), maximal common carotid IMT (CCA(max) IMT) and maximal bifurcation IMT (BIF(max) IMT) were measured bilaterally using B mode, colour Doppler ultrasonography. In stroke subjects IMT within CCA and BIF were greater than in disease controls and the percentage of PMPs prior to and after ex vivo stimulation with agonists was significantly higher than in controls. Multiple regression analysis revealed that PMPs were positively and independently correlated with both CCA(mean) IMT (ß = 0.23; p < 0.01) and stroke (ß = 0.21; p<0.01), while PAC-1 binding to platelets activated with ADP was negatively and independently associated with CCA(mean) IMT (ß = -0.29; p<0.001) and atherosclerotic carotid plaque presence (ß = -0.28, p = 0.003). We found a positive association between enhanced PMP formation and atherosclerotic thickening of carotid intima-media or carotid plaque in patients after ischaemic stroke. We demonstrated that diminished expression of active GPIIb/IIIa in the ADP-activated platelets is associated with increased carotid IMT, independently of stroke.

The hyperdense posterior cerebral artery sign in CT is related to larger ischemic lesion volume.

BACKGROUND: Hyperdensity of the middle cerebral artery (MCA) on unenhanced CT is a recognized sign associated with brain's early ischemia. The number of studies which showed a hyperdense posterior cerebral artery (HPCA) sign in posterior circulation infarct is relatively small. We investigated the prevalence of the HPCA sign, correlations with ischemic lesion volume, and stroke risk factors. We also determined the association with prothrombotic and inflammatory markers which have not been studied before. MATERIAL/METHODS: In the group of 376 patients with a first acute stroke consecutively admitted to Emergency Department, early signs of brain infarction were visible in 221 (58%) cases. Fifty five (25%) subjects had ischemic lesions in the brain supplied by the posterior circulation. We analyzed the unenhanced CT scans, calculated the density of the posterior cerebral arteries, infarct volume, and assessed the relation of the HPCA sign to other factors. RESULTS: The HPCA sign appeared on CT scans of 12 (22%) patients with evidence of the posterior circulation infarct. The density (in Hounsfield units) of the affected PCA was 46.5 comparing to 20.2 of an intact vessel (p<0.0001). The stroke volume was larger when the HPCA sign was observed (medians: 17.6 vs. 4.3 cm(3), p=0.02); in multivariate analysis this association was still significant (OR=1.07; 95% CI, 0.99-1.13). The C-reactive protein and fibrinogen levels were significantly higher (p=0.02 for both factors) in patients with the HPCA sign in the univariate analysis. CONCLUSIONS: The HPCA may be considered as an additional marker of early brain infarct, especially with large lesion volume.

Automatic segmentation of cerebrospinal fluid, white and gray matter in unenhanced computed tomography images.

RATIONALE AND OBJECTIVES: Although segmentation algorithms for cerebrospinal fluid (CSF), white matter (WM), and gray matter (GM) on unenhanced computed tomographic (CT) images exist, there is no complete research in this area. To take into account poor image contrast and intensity variability on CT scans, the aim of this study was to derive and validate a novel, automatic, adaptive, and robust algorithm. MATERIALS AND METHODS: Unenhanced CT scans of normal subjects from two different centers were used. The algorithm developed uses adaptive thresholding, connectivity, and domain knowledge and is based on heuristics on the shape of CT histogram. The slope of the intensity histogram corresponding to the three-dimensional largest connected region in a variable CSF intensity range is tracked to determine the critical intensity, which serves as an initial classifier of CSF-WM. Thresholds of CSF, WM, and GM are then optimally derived to minimize classification overlap. Multiple, null, and erroneous classifications are resolved by applying domain knowledge. RESULTS: The ground-truth regions with the minimal partial volume effect were used to evaluate segmentation results using the statistical markers. Average sensitivity, Dice index, and specificity, respectively, for the first center were 95.7%, 97.0%, and 98.6% for CSF; 96.1%, 97.3%, and 98.8% for WM; and 95.2%, 94.3%, and 92.8% for GM. The results were consistent for the second data center. CONCLUSIONS: The algorithm automatically identifies CSF, WM, and GM on unenhanced CT images with high accuracy, is robust to data from different scanners, does not require any parameter setting, and takes about 5 minutes in MATLAB to process a 512 × 512 × 30 scan. The algorithm has potential use in research and clinical applications.

Automatic model-guided segmentation of the human brain ventricular system from CT images.

RATIONALE AND OBJECTIVES: Accurate segmentation of the brain ventricular system on computed tomographic (CT) imaging is useful in neurodiagnosis and neurosurgery. Manual segmentation is time consuming, usually not reproducible, and subjective. Because of image noise, low contrast between soft tissues, large interslice distance, large shape, and size variations of the ventricular system, no automatic method is presently available. The authors propose a model-guided method for the automated segmentation of the ventricular system. MATERIALS AND METHODS: Fifty CT scans of patients with strokes at different sites were collected for this study. Given a brain CT image, its ventricular system was segmented in five steps: (1) a predefined volumetric model was registered (or deformed) onto the image; (2) according to the deformed model, eight regions of interest were automatically specified; (3) the intensity threshold of cerebrospinal fluid was calculated in a region of interest and used to segment all regions of cerebrospinal fluid from the entire brain volume; (4) each ventricle was segmented in its specified region of interest; and (5) intraventricular calcification regions were identified to refine the ventricular segmentation. RESULTS: Compared to ground truths provided by experts, the segmentation results of this method achieved an average overlap ratio of 85% for the entire ventricular system. On a desktop personal computer with a dual-core central processing unit running at 2.13 GHz, about 10 seconds were required to analyze each data set. CONCLUSION: Experiments with clinical CT images showed that the proposed method can generate acceptable results in the presence of image noise, large shape, and size variations of the ventricular system, and therefore it is potentially useful for the quantitative interpretation of CT images in neurodiagnosis and neurosurgery.